DOSAGE & INDICATIONS

For the treatment of serious gram-positive infections, including lower respiratory tract infections such as pneumonia, community-acquired pneumonia (CAP), nosocomial pneumonia, and pleural empyema.

Intravenous dosage (Intermittent IV Infusion)

Adults

25 to 30 mg/kg IV loading dose for seriously-ill patients, then 15 to 20 mg/kg IV every 8 to 12 hours in combination with other appropriate antibiotics per clinical practice guidelines. Alternately, FDA-approved labeling suggests 2 g/day IV divided either as 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations. For MRSA, clinical practice guidelines recommend a treatment duration of 7 to 21 days for pneumonia. For community-acquired pneumonia (CAP), treat for at least 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 CAP-associated sign of clinical instability before discontinuing therapy. A longer duration may be needed if the initial therapy is not active against identified pathogens or if there are complications.For nosocomial pneumonia, treat for 7 days. Clinical practice guidelines recommend empiric vancomycin use in patients with risk factors for MRSA. For hospital-acquired or postprocedural empyema, use vancomycin in combination with piperacillin; tazobactam or metronidazole and cefepime for a minimum of 2 weeks after drainage and defervescence.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by The Infectious Diseases Society of America (IDSA) for infections caused by MRSA; a loading dose of 20 to 25 mg/kg/dose may be considered in seriously ill pediatric patients. Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV in divided doses every 6 hours ; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive methicillin-resistant Staphylococcus aureus (MRSA) infections, and those with malignancy. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study. For MRSA, the IDSA recommends to treat for 7 to 21 days for pneumonia, with a duration of 10 days for community-acquired pneumonia (CAP).

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, the IDSA recommends to treat for 7 to 21 days for pneumonia.

Intravenous dosage (Continuous IV Infusion)†

NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients ; the role of continuous infusion administration in pediatric patients is unclear.

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into two distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

Infants, Children, and Adolescents

A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

Neonates

A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

For the treatment of infective endocarditis.

Intravenous dosage

Adults

15 to 20 mg/kg/dose IV every 8 to 12 hours is recommended by clinical practice guidelines. Adjust dosage based on serum concentrations. For seriously-ill patients, consider a loading dose of 25 to 30 mg/kg IV. The FDA-approved dosage is 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Clinical practice guidelines recommend vancomycin monotherapy for 4 weeks for native valve endocarditis (NVE) due to highly penicillin-susceptible Viridans group streptococci (VGS) and S. gallolyticus (bovis) infections or relatively penicillin-resistant VGS for patients unable to tolerate penicillins or ceftriaxone as well as penicillin-resistant VGS infections. Treat prosthetic valve endocarditis (PVE) caused by VGS for 6 weeks. Vancomycin may be used for 4 weeks for NVE and for 6 weeks for PVE caused by S. pneumoniae for patients intolerant of beta-lactams. Consider adding vancomycin and rifampin to cefotaxime or ceftriaxone for infections due to cefotaxime-resistant S. pneumoniae. Vancomycin for 4 to 6 weeks is an alternative for infections due to S. pyogenes in patients intolerant to beta-lactams. Vancomycin is also recommended for 6 weeks for NVE due to staphylococci for patients with anaphylactoid-type hypersensitivity reactions to beta-lactams or methicillin-resistant strains. Vancomycin plus rifampin for at least 6 weeks and gentamicin for 2 weeks is recommended for PVE caused by methicillin-resistant staphylococci. Use vancomycin plus gentamicin for 6 weeks for NVE or PVE due to penicillin-resistant Enterococcus in patients unable to tolerate a beta-lactam. For patients with acute (days) culture-negative NVE, vancomycin plus cefepime could be reasonable empiric therapy, and for patients with subacute (weeks) culture-negative NVE, vancomycin plus ampicillin; sulbactam could be reasonable empiric therapy. For patients with early (less than 1 year after surgery) culture-negative PVE, vancomycin plus cefepime, rifampin, and gentamicin could be reasonable empiric therapy, and for late culture-negative PVE, an initial treatment option could include ceftriaxone and vancomycin. Treat culture-negative endocarditis for 4 to 6 weeks.

Children and Adolescents

40 to 60 mg/kg/day IV divided every 6 to 12 hours is recommended by clinical practice guidelines. Adjust dosage based on serum concentrations. For seriously-ill patients, consider a loading dose of 25 to 30 mg/kg IV. The FDA-approved dosage for pediatric patients is 40 mg/kg/day IV divided every 6 hours. Clinical practice guidelines recommend gentamicin plus ampicillin; sulbactam with or without vancomycin for culture-negative, community-acquired native valve endocarditis (NVE) or late (more than 1 year after surgery) prosthetic valve endocarditis (PVE); alternately, vancomycin plus gentamicin may be used. Treat for 4 to 6 weeks for NVE and for 6 weeks with rifampin for PVE. Vancomycin plus gentamicin, cefepime, and rifampin (if prosthetic material is present) is recommended for culture-negative nosocomial endocarditis associated with vascular cannulae or early (less than 1 year after surgery) PVE; treat for 4 to 6 weeks, with a longer course for PVE. For endocarditis due to relatively penicillin-resistant streptococci, including enterococci, vancomycin, in combination with gentamicin for the first 2 weeks or the entire course for enterococci, is recommended as an alternative; vancomycin is also an alternative for streptococcal endocarditis highly susceptible to penicillin. For streptococcal endocarditis, treat for 4 weeks for NVE and 6 weeks for PVE; treat for 6 weeks for NVE and PVE due to enterococci. Vancomycin, with or without gentamicin for the first 3 to 5 days, is recommended for methicillin-resistant S. aureus endocarditis; vancomycin, with or without gentamicin for the first 3 to 5 days, is an alternative for staphylococcal endocarditis susceptible to or resistant to penicillin G. Add rifampin (for the entire course) plus gentamicin (for the first 2 weeks of therapy) for staphylococcal PVE. For native valve staphylococcal endocarditis susceptible to oxacillin, treat for 4 to 6 weeks. For native valve staphylococcal endocarditis resistant to oxacillin or prosthetic valve staphylococcal endocarditis, treat for at least 6 weeks.

Infants

60 mg/kg/day IV divided every 6 hours in combination with appropriate antimicrobial therapy depending on causative microorganism is recommended by clinical practice guidelines. For seriously-ill patients, a loading dose of 25 to 30 mg/kg IV may be considered. Adjust dosage based on serum concentrations. The FDA-approved dosage for pediatric patients is 40 mg/kg/day IV divided every 6 hours.

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.

For the treatment of pseudomembranous colitis due to Clostridium difficile. NOTE: Oral administration is required for this condition. For patients who are unable to swallow capsules, the IV product may be used orally, there is an oral powder for solution, or an extemporaneous solution can be compounded from the oral capsule. NOTE: The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) recommend that initial mild-moderate cases of C. difficile infection be treated with metronidazole.

Oral dosage

Adults

The manufacturer recommends 125 mg PO 4 times daily for 10 days. The IDSA and SHEA recommend 125 mg PO 4 times daily for 10 to 14 days for initial episodes of severe C. difficile infections (CDI). For severe, complicated CDI (hypotension, shock, ileus, megacolon), IDSA/SHEA recommend 500 mg PO 4 times daily with or without IV metronidazole (500 mg IV every 8 hours). If there is a complete ileus, consider adding vancomycin as a retention enema every 6 hours. Treatment of first recurrence of CDI is usually with the same regimen used for the initial episode, but should be stratified by disease severity. Subsequent CDI episodes should be treated with vancomycin using a tapered and/or pulse regimen. IDSA/SHEA states various pulse regimens have been used and recommend this regimen as an option: 125 mg PO 4 times daily for 10 to 14 days, then 125 mg PO 2 times daily for 1 week, then 125 mg PO once daily for 1 week, then 125 mg every 2 to 3 days for 2 to 8 weeks. In patients with multiple relapses of C. difficile, the following 6-week tapered regimen has also been successful: week 1, 125 mg PO four times daily; week 2, 125 mg PO twice daily; week 3, 125 mg PO once daily; week 4, 125 mg PO every other day; and weeks 5 to 6, 125 mg PO every 3 days.

Infants, Children, and Adolescents

Although the manufacturer states that safety and efficacy have not been established in pediatrics, they recommend 40 mg/kg/day PO in 3 to 4 divided doses for 7 to 10 days (Max: 2 g/day). For C. difficile infection (CDI), the American Academy of Pediatrics (AAP) recommends 40 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for at least 10 days. The AAP recommends metronidazole as first-line therapy for mild to moderate CDI and oral vancomycin with or without IV metronidazole for severe CDI or second recurrence.

Rectal dosage†

Adults

500 mg in approximately 100 mL of 0.9% Sodium Chloride Injection per rectum as a retention enema every 6 hours is suggested as adjunctive therapy with oral vancomycin with or without IV metronidazole by the IDSA/SHEA in patients with a complete ileus. Other dosing regimens have been described in case reports including 500 mg every 4 hours and 1 g every 8 to 12 hours. Volumes of 250 to 500 mL of 0.9% Sodium Chloride Injection have also been described. Decompression of the megacolon may also be beneficial.

Infants, Children, and Adolescents

Rectal vancomycin is suggested as adjunctive therapy with oral vancomycin with or without IV metronidazole by the IDSA/SHEA, as well as the American Academy of Pediatrics (AAP), in patients with severe or complicated disease (i.e., ileus, megacolon, hypotension or shock); however, very limited dosing data are available in pediatric patients. One case report in a 4-year-old boy with toxic megacolon due to C. difficile infection describes the use of rectal vancomycin 125 mg in 25 mL of 0.9% Sodium Chloride Injection given four times daily. Intracolic vancomycin was continued for a total treatment duration of 1 month. Decompression of the megacolon may also be beneficial. A rectal vancomycin dose of 500 mg in 100 mL 0.9% Sodium Chloride Injection every 6 hours is recommended by the IDSA/SHEA in adult patients. Other dosing regimens have been described in case reports in adults including 500 mg every 4 to 8 hours and 1 g every 8 to 12 hours. These doses/volume (i.e., 500 mg in 100 mL 0.9% Sodium Chloride Injection) may be acceptable for older children and adolescents of appropriate weight.

For the treatment of enterocolitis due to Staphylococcus aureus. NOTE: Oral administration is required for this condition. For patients who are unable to swallow capsules, the IV product may be used orally, there is an oral powder for solution, or an extemporaneous solution can be compounded from the oral capsule.

Oral dosage

Adults

500 mg to 2 g PO per day given in 3 to 4 divided doses for 7 to 10 days.

Infants, Children, and Adolescents

Although the manufacturer states that safety and efficacy have not been established in pediatric patients, 40 mg/kg/day (Max: 2 g/day) PO in 3 to 4 divided doses for 7 to 10 days is recommended in the full prescribing information.

For the treatment of serious gram-positive infections, including bacteremia and sepsis.

Intravenous dosage (Intermittent IV Infusion)

Adults

25 to 30 mg/kg IV loading dose, then 15 to 20 mg/kg IV every 8 to 12 hours per clinical practice guidelines. Alternately, FDA-approved labeling suggests 2 g/day IV divided either as 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. Start within 1 hour of recognition as part of empiric multi-drug therapy. Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response. For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia. The addition of gentamicin or rifampin is not recommended for bacteremia.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by The Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg/dose may be considered in seriously ill pediatric patients. Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV in divided doses every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study. For MRSA, the IDSA recommends to treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, the IDSA recommends to treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.

Intravenous dosage (Continuous IV Infusion)†

NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

Infants, Children, and Adolescents

A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

Neonates

A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations.

For the treatment of serious gram-positive infections, including skin and skin structure infections, such as cellulitis.

Intravenous dosage (Intermittent IV Infusion)

Adults

The manufacturer recommends 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. They also suggest these doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Doses should be adjusted based on serum concentrations. For seriously-ill patients, these groups suggest a loading dose of 25 to 30 mg/kg (based on actual body weight) IV. The panel also states that conventional dosing nomograms will likely not lead to appropriate trough serum concentrations. The ASHP, IDSA, and SIDP suggest using actual body weight for dosing even in obese patients; however, they note that doses should be altered based on serum concentrations. For MRSA, the IDSA recommends to treat for 7 to 14 days for complicated skin and skin structure infections. Extended dosing intervals are usually required in those with renal impairment.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by The Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg/dose may be considered in seriously ill pediatric patients. Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV in divided doses every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study. For MRSA, the IDSA recommends to treat for 7 to 14 days for complicated skin and skin structure infections.

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, the IDSA recommends to treat for 7 to 14 days for complicated skin and skin structure infections.

Intravenous dosage (Continuous IV Infusion)†

NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

Infants, Children, and Adolescents

A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

Neonates

A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

For surgical infection prophylaxis†.

Intravenous dosage

Adults

15 mg/kg IV as a single dose within 120 minutes prior to the surgical incision. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend vancomycin as alternate therapy for patients with beta-lactam allergy undergoing cardiothoracic, hernia repair, neurosurgical, orthopedic, clean urologic, vascular, heart or lung transplantation, and plastic surgery procedures. Vancomycin is also recommended in combination with another appropriate antimicrobial (i.e., aminoglycoside, aztreonam, or fluoroquinolone) as alternate therapy for patients with beta-lactam allergy undergoing gastroduodenal, biliary tract, hysterectomy, urologic with prosthesis, and abdominal transplantation procedures.

Infants, Children, and Adolescents

15 mg/kg IV as a single dose within 120 minutes prior to the surgical incision. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend vancomycin as alternate therapy for patients with beta-lactam allergy undergoing cardiothoracic, hernia repair, neurosurgical, orthopedic, clean urologic, vascular, heart or lung transplantation, and plastic surgery procedures. Vancomycin is also recommended in combination with another appropriate antimicrobial (i.e., aminoglycoside, aztreonam, or fluoroquinolone) as alternate therapy for patients with beta-lactam allergy undergoing gastroduodenal, biliary tract, urologic with prosthesis, and abdominal transplantation procedures.

25 to 30 mg/kg IV loading dose, then 15 to 20 mg/kg IV every 8 to 12 hours. Adjust doses based on serum concentrations. Doses should be aggressive due to the relatively poor penetration of vancomycin into cerebral spinal fluid (CSF). Treat with or without rifampin for 2 weeks for MRSA meningitis. For other MRSA-associated CNS infections, including brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus, the treat with or without rifampin for 4 to 6 weeks.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by the Infectious Diseases Society of America (IDSA); adjust dosage based on serum concentrations. A loading dose of 20 to 25 mg/kg may be considered in seriously ill pediatric patients. Treat for 2 weeks for meningitis or for 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years), the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.

Neonates

20 to 30 mg/kg/day IV in divided doses every 8 to 12 hours for neonates 0 to 7 days weighing 2 kg or more or 30 to 45 mg/kg/day IV in divided doses every 6 to 8 hours for neonates more than 7 days weighing 2 kg or more is recommended by IDSA. Alternatively, the American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 2 weeks for meningitis or for 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus.

5 to 20 mg/day intraventricularly is recommended by the Infectious Diseases Society of America (IDSA); however, they state that most studies have used a 10 mg or 20 mg dose. Use in addition to systemic vancomycin therapy. Adjust intrathecal or intraventricular dosage as necessary based on vancomycin CSF concentrations and MIC of the organism.

Infants, Children, and Adolescents

5 to 20 mg/day intraventricularly is recommended by the Infectious Diseases Society of America (IDSA); however, they state that most studies have used a 10 mg or 20 mg dose. Use in addition to systemic vancomycin therapy. Adjust intrathecal or intraventricular dosage as necessary based on vancomycin CSF concentrations and MIC of the organism.

For vancomycin desensitization† in patients with vancomycin hypersensitivity who require vancomycin therapy. NOTE: Several different vancomycin desensitization protocols have been reported in the literature and are based on case reports or small case series. Two methods are noted below.NOTE: Once the desensitization process is complete, do not miss scheduled vancomycin doses to avoid drug-free periods or the desensitization process will have to be repeated. Desensitization is required prior to any subsequent vancomycin use in hypersensitive patients as desensitization does not extend beyond the time frame that vancomycin has been stopped.NOTE: Concomitant use of medications that may induce histamine response may lead to unsuccessful desensitization and the use of these medications should be temporarily withheld, changed to an alternative, or given in restricted amounts. Medications that are potential histamine inducers included ciprofloxacin, barbiturates, narcotic analgesics (fentanyl may only rarely induce histamine), neuromuscular antagonists (succinylcholine and benzylisoquinoline compounds, not steroidal compounds), propofol, plasma expanders (dextran, polygeline), and radiocontrast agents.

Slow vancomycin desensitization† protocol (Lin method). NOTE: This method has been used when rapid desensitization has failed.NOTE: Another case report showed a modified version of the Lin desensitization protocol that stretched the procedure out to 13 days when the patient reported adverse events during the slow desensitization process.

For perinatal Group B streptococcal bacterial infection prophylaxis† in patients allergic to penicillins and cephalosporins.

Intravenous dosage

Pregnant adult females

1 g IV every 12 hours intrapartum, at the time of labor or rupture of membranes until delivery, in patients allergic to penicillin and cephalosporins who have isolates resistant to clindamycin. Penicillin is the agent of choice for preventing Group B streptococcal disease. Antibiotics administered for at least 4 hours before delivery have been found to be highly effective at preventing the transmission of Group B Streptococcus.

For the treatment of bone and joint infections, including osteomyelitis and septic/infectious arthritis, or an orthopedic device-related infection†.

For the treatment of osteomyelitis.

Intravenous dosage

Adults

The manufacturer recommends 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. They also suggest that these doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust doses based on serum concentrations. For seriously-ill patients, these groups suggest a loading dose of 25 to 30 mg/kg (based on actual body weight) IV. The panel also states that conventional dosing nomograms will likely not lead to appropriate trough serum concentrations. ASHP, IDSA, and SIDP suggest using actual body weight for dosing even in obese patients; however, they note that doses should be altered based on serum concentrations. For MRSA, IDSA suggests that rifampin 600 mg PO daily or 300 to 450 mg PO twice daily may be added; however, in patients with concurrent bacteremia, rifampin should be added after the clearance of the bacteremia. A minimum duration of 8 weeks is recommended; however, an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus either sulfamethoxazole; trimethoprim, doxycycline, minocycline, clindamycin, or a fluoroquinolone may be necessary. Extended dosing intervals are usually required in those with renal impairment.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by The Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg/dose may be considered in seriously ill pediatric patients. Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV in divided doses every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study. For MRSA, the IDSA recommends to treat for at least 4 to 6 weeks.

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, the IDSA recommends to treat for at least 4 to 6 weeks.

Intravenous dosage (Continuous IV Infusion)†

NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

Infants, Children, and Adolescents

A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

Neonates

A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

For the treatment of septic arthritis.

Intravenous dosage

Adults

The manufacturer recommends 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. They also suggest that these doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Doses should be adjusted based on serum concentrations. For seriously-ill patients, these groups suggest a loading dose of 25 to 30 mg/kg (based on actual body weight) IV. The panel also states that conventional dosing nomograms will likely not lead to appropriate trough serum concentrations. The ASHP, IDSA, and SIDP suggest using actual body weight for dosing even in obese patients; however, they note that doses should be altered based on serum concentrations. For MRSA, the IDSA recommends a treatment duration of at least 3 to 4 weeks. Extended dosing intervals are usually required in those with renal impairment.

Infants, Children, and Adolescents

60 mg/kg/day IV in divided doses every 6 hours is recommended by The Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg/dose may be considered in seriously ill pediatric patients. Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV in divided doses every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy. Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study. For MRSA, the IDSA recommends to treat for at least 3 to 4 weeks.

Neonates

The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The American Academy of Pediatrics (AAP) recommends the following general dosing schedule based on serum creatinine (SCr) concentration, which will take approximately 5 days from birth to reasonably reflect neonatal renal function: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, the IDSA recommends to treat for at least 3 to 4 weeks.

Intravenous dosage (Continuous IV Infusion)†

NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

Infants, Children, and Adolescents

A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

Neonates

A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

For the treatment of prosthetic joint infections.

Intravenous dosage

Adults

The manufacturer recommends 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. They also suggest that these doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Doses should be adjusted based on serum concentrations. For seriously-ill patients, these groups suggest a loading dose of 25 to 30 mg/kg (based on actual body weight) IV. The panel also states that conventional dosing nomograms will likely not lead to appropriate trough serum concentrations. The ASHP, IDSA, and SIDP suggest using actual body weight for dosing even in obese patients; however, they note that doses should be altered based on serum concentrations. For MRSA, the IDSA recommends the addition of rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours for 2 weeks in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus a fluoroquinolone, sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin) should start after the completion of IV therapy and continue for 3 months for hip infections or for 6 months for knee infections. Extended dosing intervals are usually required in those with renal impairment.

Intravenous dosage (Continuous IV Infusion)†

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients. NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions.

For the treatment of spinal implant infections.

Intravenous dosage

Adults

The manufacturer recommends 2 g/day IV divided either as 500 mg every 6 hours or 1 g every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. They also suggest that these doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Doses should be adjusted based on serum concentrations. For seriously-ill patients, these groups suggest a loading dose of 25 to 30 mg/kg (based on actual body weight) IV. The panel also states that conventional dosing nomograms will likely not lead to appropriate trough serum concentrations. The ASHP, IDSA, and SIDP suggest using actual body weight for dosing even in obese patients; however, they note that doses should be altered based on serum concentrations. For MRSA, the IDSA recommends the addition of rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy (sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin with or without rifampin, or a fluoroquinolone plus rifampin) should follow parenteral therapy; however, the optimal duration of parenteral and/or oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible. Extended dosing intervals are usually required in those with renal impairment.

Intravenous dosage (Continuous IV Infusion)†

Adults

There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients. NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions.

For the empiric treatment of febrile neutropenia†.

Intravenous dosage

Adults

500 mg to 1,000 mg IV every 8 to 12 hours or 15 mg/kg IV every 12 hours has been studied. Guidelines suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. Doses should be adjusted based on serum concentrations. Febrile neutropenia guidelines suggest vancomycin should be added in patients at increased risk for MRSA or enterococcal infections.

For the treatment of peritoneal dialysis-associated peritonitis† in patients with end-stage renal disease.

Intraperitoneal dosage

Adults

The International Society for Peritoneal Dialysis (ISPD) recommends the following dosage options: CONTINUOUS THERAPY: 1,000 mg/L in peritoneal dialysate as a loading dose followed by a maintenance dose of 25 mg/L in each dialysate exchange. INTERMITTENT THERAPY: 15 to 30 mg/kg/dose administered in the first peritoneal dialysate exchange bag, and then every 5 to 7 days. Allow the dialysate containing vancomycin to dwell for at least 6 hours. In patients with residual renal function (defined as more than 100 mL/day urine output), the dose should be empirically increased by 25%. For intermittent dosing in automated peritoneal dialysis, administer 30 mg/kg IP in the long dwell, and repeat dosing of 15 mg/kg IP in the long dwell every 3 to 5 days based on serum concentrations.

Infants, Children, and Adolescents

The International Society for Peritoneal Dialysis (ISPD) recommends the following dosage options: CONTINUOUS THERAPY: 1,000 mg/L in peritoneal dialysate as a loading dose followed by a maintenance dose of 25 mg/L in each dialysate exchange. For the loading dose, allow a dwell time of 3 to 6 hours; after the loading dose, all other exchanges should contain the maintenance dose. INTERMITTENT THERAPY: 30 mg/kg/dose administered in the first peritoneal dialysate exchange bag, and then 15 mg/kg/dose every 3 to 5 days. Administer doses during the long-dwell. Patients with residual renal function may have increased elimination of vancomycin when administered as an intermittent dose; therefore, obtain a vancomycin serum concentration in these patients 2 to 4 days after the initial dose to establish the frequency of the dosing regimen.

For the treatment of systemic anthrax† infection.

Intravenous dosage

Adults

60 mg/kg/day IV divided every 8 hours. Maintain vancomycin serum trough concentrations of 15 to 20 mg/L. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in adults. Treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required.

Infants, Children, and Adolescents

60 mg/kg/day IV divided every 8 hours. Adjust dose based on vancomycin serum concentrations. Vancomycin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with vancomycin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with vancomycin, a fluoroquinolone, and a protein synthesis inhibitor is recommended. For systemic infection in which meningitis can be excluded, treatment should continue for at least 14 days or until clinical criteria for improvement are met. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

Neonates 32 weeks gestation and older

Initiate treatment with a 20 mg/kg IV loading dose, followed by initial dosing based on serum creatinine concentrations: SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours; SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours; SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours; SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours; SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Adjust dose based on vancomycin serum concentrations. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in neonates. Treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required.

older than 7 days: 30 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.0 to 7 days: 20 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.

DOSING CONSIDERATIONS

Hepatic Impairment

Dosage adjustment not required.

Renal Impairment

The manufacturer’s renal adjustment recommendations and conventional dosing nomograms will likely not lead to appropriate trough serum concentrations as defined by the 2009 American Society of Health-System Pharmacists (ASHP), Infectious Diseases Society of America (IDSA), and Society of Infectious Diseases Pharmacists (SIDP) expert panel. As recommended by this expert panel, an initial 15 to 20 mg/kg IV dose (or a 25 to 30 mg/kg IV loading dose in seriously ill patients) should be used. However, in renally impaired patients, the initial dosing interval should be individualized based on specific patient and disease-state characteristics, serum concentration goals, site of infection, weight, age, and degree and stability of renal impairment (acute versus chronic). Further dosing should be guided by serum vancomycin concentrations.

Intermittent hemodialysisVancomycin is not significantly removed during a standard intermittent hemodialysis session using conventional cuprophane membranes. After an initial dose of 15 mg/kg IV, serum vancomycin concentrations should be used to guide further dosing. In general, hemodialysis removes varying degrees of vancomycin, a 1,500-Dalton molecule, depending on the type of filter used. Low flux membranes do not remove much vancomycin, leading to the traditional once-weekly dosing of vancomycin. If high-flux polysulfone dialysis membranes are used, more significant amounts of vancomycin may be removed (26% to 50%) and a supplemental dose after dialysis may be necessary. Hemodialysis filter type should be considered when determining vancomycin clearance. Due to redistribution of vancomycin after the high-flux dialysis procedure, dosage supplementation should be based on serum concentrations obtained at least 12 hours after the end of the procedure.

Continuous renal replacement therapy (i.e., CAVH, CVVH, CVVHD, CVVHDF)Definitive dosage recommendations have not been established. Vancomycin clearance during continuous renal replacement therapy (CRRT) depends on the specific type of CRRT used, including continuous arteriovenous hemofiltration (CAVH), continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF). Clearance also depends on the sieving coefficient (SC) for vancomycin for the filter membranes, the CRRT ultrafiltrate rate, the patient's residual renal function, the volume of distribution, the fraction of drug unbound to plasma proteins, and the duration of the CRRT per day. In general, there may be 50% to 60% of the vancomycin dose removed during CRRT. Proposed doses for patients receiving CVVH have ranged from 500 mg IV every 24 hours to 1,500 mg IV every 48 hours. Doses for patients receiving CVVHD or CVVHDF have ranged from 1 to 1.5 g IV every 24 hours. Loading dose of 15 to 20 mg/kg IV should be used in these patients. Any dosing recommendations should be approached with caution as the CRRT methods may vary between institutions. Additional patient and disease-state factors should also be considered and dosing should be guided by individual patient vancomycin serum concentrations.

Peritoneal dialysisClearance of vancomycin by intermittent peritoneal dialysis is highly variable; when administering vancomycin intravenously, supplemental dosing may be necessary to maintain adequate serum concentrations. For intraperitoneal dosing, see dosage guidelines for the treatment of peritoneal dialysis-associated peritonitis in patients with end-stage renal disease.

ADMINISTRATION

Oral Administration

Oral Solid Formulations

May be administered with or without food. Swallow whole; do not crush or chew.

Oral Liquid Formulations

Powder for oral solution: Shake well prior to each administration. Measure dosage with calibrated spoon, cup, or oral syringe.Avoid contact with eyes.

Reconstitution method for the powder for oral solution:Available as a compounding kit containing one bottle of vancomycin powder and one bottle of grape solution.Various bottle sizes are available which, when reconstituted, produce either a 25 mg/mL or 50 mg/mL vancomycin oral solution. Select the appropriate bottle size/concentration for the individual patient.Remove the cap from the bottle containing the vancomycin powder. Tap the top of the induction seal to loosen the powder. Slowly peel back the foil seal.Shake the bottle containing grape solution for a few seconds prior to removing the cap. Open the bottle and empty all of the contents into the vancomycin powder bottle. Replace the cap and shake the mixture vertically for approximately 30 seconds.Storage after reconstitution: Store under refrigeration at 2 to 8 degrees C (36 to 46 degrees F); DO NOT freeze. Discard any unused solution after 30 days. Keep container tightly closed and protect from light.

Extemporaneous Compounding-Oral

If the patient is unable to swallow the capsule, the capsule contents may be dispersed in water for administration. Use a sharp knife or similar instrument to remove the outer shell of the capsule; the inner contents will be solid. Dissolve the solid inner contents of the capsule with approximately 2 tablespoons of warm water (37 degrees C or 98 degrees F); the time for dissolution should not exceed 30 minutes. Orange juice or another acidic vehicle may be added to improve palatability. Prepare the dispersion just prior to administration. Administer orally or via a nasogastric tube.If the patient is unable to swallow capsules, the vancomycin powder for injection (not including ADD-Vantage vials) may be used for enteral administration. Dilute the appropriate dose in 1 oz of water. Common flavoring syrups may be added to the solution to improve palatability. Prepare the solution just prior to administration. Administer orally or via a nasogastric tube.

Powder vials for injection:Reconstitution:Reconstitute 500 mg or 1 g powder vials with 10 or 20 mL, respectively, of Sterile Water for Injection to give a solution containing 50 mg/mL.FURTHER DILUTION IS REQUIRED BEFORE ADMINISTRATION.Storage: Reconstituted vials may be stored in the refrigerator for up to 14 days.Dilution:Further dilute 500 mg or 1 g reconstituted solutions with at least 100 mL or at least 200 mL, respectively, of a compatible IV solution.Concentrations of 5 mg/mL are recommended; however, concentrations of up to 10 mg/mL may be used in patients in need of fluid restriction. Higher concentrations may increase the risk of infusion-related reactions.Solutions diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may be stored in the refrigerator for up to 14 days.Storage: Solutions diluted with 5% Dextrose Injection/0.9% Sodium Chloride Injection, Lactated Ringer's Injection, Lactated Ringer's/5% Dextrose Injection, Normosol-M, or Isolyte E maybe be stored in the refrigerator for up to 96 hours.

Bulk vials for injection:Reconstitution:5 g bulk vials: Reconstitute with 100 mL of Sterile Water for Injection to give a solution containing 500 mg/10 mL (50 mg/mL).10 g bulk vials: Reconstitute with 95 mL of Sterile Water for Injection to give a solution containing 500 mg/5 mL (100 mg/mL).The bulk vial should be penetrated one time with a suitable sterile dispensing set that allows measured distribution of the contents. The entire contents of the bulk vial should be used during reconstitution.Storage: Once penetration of the bulk vial has occurred with a sterile dispensing set, withdrawal of the contents should be done promptly. A maximum of 4 hours from initial penetration may be allowed to complete fluid aliquoting/transferring operations before discarding the container.FURTHER DILUTION IS REQUIRED. Dilution:Dilute reconstituted solution with an appropriate diluent to a final concentration of 5 mg/mL (i.e., 500 mg diluted in 100 mL of diluent, 1 g diluted in 200 mL of diluent).Concentrations of 5 mg/mL are recommended; however, concentrations of up to 10 mg/mL may be used in patients in need of fluid restriction. Higher concentrations may increase the risk of infusion-related reactions.Appropriate diluents include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection/0.9% Sodium Chloride Injection, Lactated Ringer's Injection, Lactated Ringer's/5% Dextrose Injection, Normosol-M and 5% Dextrose Injection, and Isolyte E.Storage: Specific storage instructions after dilution are not provided in the FDA-approved labeling for bulk products. The labeling states that compounded admixtures should be used as soon as feasible. The vancomycin 1 g vials product labeling states that solutions diluted in 5% Dextrose Injection or 0.9% Sodium Chloride Injection are stable for 96 hours refrigerated.

ADD-Vantage IV solution:Reconstitution:Reconstitute only with 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the appropriate flexible diluent container provided. For 500 mg vials, use at least a 100 mL diluent container and for 750 mg and 1 g vials, use only the 250 mL diluent container.Remove the protective covers from the top of the vial and vial port. Remove vial cap (do not access with a syringe) and vial port cover. Screw the vial into the vial port until it will go no further to assure a seal. Once vial is sealed to the port, do not remove. To activate the contents of the vial, squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial. With the other hand, push the drug vial down into the container telescoping walls of the container and grasp the inner cap of the vial through the walls of the container. Pull the inner cap from the drug vial. Verify the rubber stopper has been pulled out, allowing the drug and diluent to mix. Mix the container contents thoroughly.Storage: The admixture solution may be stored for up to 24 hours at room temperature or in the refrigerator for up to 14 days.Do not use in series connections with flexible containers.

Pre-mixed Galaxy IV solution:Preparation:Thaw frozen containers at room temperature (25 degrees C or 77 degrees F) or under refrigeration (5 degrees C or 41 degrees F). Do not force thaw by immersion in water baths or by microwave irradiation. Check for leaks by squeezing bag firmly.Do not add supplementary medication.Contents of the solution may precipitate in the frozen state and should dissolve with little or no agitation once the solution has reached room temperature.Storage: The thawed solution is stable for 72 hours at room temperature or for 30 days under refrigeration. Do not refreeze thawed product.Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Intermittent IV Infusion Administration:Infuse appropriate dose over at least 1 hour to reduce the risk of infusion-related reactions. Infusion rates of up to 10 mg/minute are recommended by the manufacturer.

Continuous IV infusion:NOTE: Vancomycin is not approved by the FDA to be administered by continuous IV infusion.NOTE: The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) state that continuous infusion vancomycin holds no advantage over intermittent infusions.Several dosage regimens have been discussed in the literature and there is no consensus on dose and administration volume.Continuous infusion regimens usually start after an initial loading dose. Doses of 1 to 2 g of vancomycin in 1000 mL of 0.9% Sodium Chloride Injection and 2 g of vancomycin in 250 mL of 5% Dextrose Injection, both administered over 24 hours, have been utilized in adults. One study in neonates diluted vancomycin in 5% Dextrose Injection to achieve a 5 mg/mL continuous infusion concentration. This was administered without a loading dose.

Retention Enema (using intravenous product)Doses of 500 mg to 1 g diluted in volumes of 100 to 500 mL of 0.9% Sodium Chloride Injection have been utilized. While no specific dilution instructions have been described, preparation of the enema per the instructions associated with each specific powder for injection product would seem warranted.Stability should coincide with specific intravenous product labeling.

Instillation:While the IDSA/SHEA guidelines do not give specific instillation recommendations, a method of instilling the dose over 15 minutes with clamping of the tube for 1 to 2 hours has been described. Specific patient circumstances will likely dictate the duration of the dwell.

CONTRAINDICATIONS / PRECAUTIONS

Vancomycin therapy may result in superinfection with non susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.

Corn hypersensitivity, vancomycin hypersensitivity

Vancomycin is contraindicated in patients who have a history of vancomycin hypersensitivity. Vancomycin solutions containing dextrose may be contraindicated in patients with history of corn hypersensitivity or corn product hypersensitivity.

Viral infection

This drug does not treat viral infection (e.g., common cold). Prescribing vancomycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier.

Nephrotoxicity, renal disease, renal failure, renal impairment

Vancomycin should be used with caution in patients with renal impairment because it can accumulate. Doses should be adjusted in patients with renal dysfunction. Vancomycin serum concentrations and renal-function tests should be performed during therapy, especially when concurrent nephrotoxic agents, such as aminoglycosides, are used. Nephrotoxicity (renal failure), principally manifested by azotemia (increased BUN) or increased serum creatinine, has been rarely reported with vancomycin. The risk for nephrotoxicity is increased in patients receiving large doses of vancomycin, in those receiving other nephrotoxic drugs such as aminoglycosides, or those who had preexisting renal disease or impairment. Historically, nephrotoxicity may be associated with product impurity. As monotherapy, nephrotoxicity associated with vancomycin in the literature is reported to be 5 to 7% or less. Vancomycin does potentiate the nephrotoxic effects of aminoglycosides and may increase that potential by 3- to 4-fold. Vancomycin exposure to renal proximal tubule epithelial cells results in increased oxygen consumption and ATP concentrations. Toxicity is not limited to the proximal tubules, but may also involve the medullary regions (loop of Henle and collecting duct) of the nephron. Vancomycin toxicity resulting in the destruction of glomeruli and proximal tubule necrosis may be due to oxidative stress. Nephrotoxicity due to vancomycin monotherapy is usually reversible. Higher doses have been associated with nephrotoxicity in some studies; however, concomitant nephrotoxic agents, severity of illness, patient hemodynamics, and the use of pressors may all complicate the interpretation of nephrotoxicity in these patients. Additionally, it is often difficult to determine if higher vancomycin concentrations preceded nephrotoxicity or were a result of worsening renal impairment.

Administer each intravenous vancomycin dose over a period of at least 60 minutes; too-rapid administration can lead to infusion-related reactions such as 'red man syndrome'. The frequency of infusion-related events may be higher with the concomitant administration of anesthetic agents. In addition, care must be taken to avoid extravasation because vancomycin is extremely irritating to tissues. Avoid intramuscular administration due to severe pain at the injection site. The safety and efficacy of intrathecal administration (intralumbar or intraventricular), intraperitoneal administration, intracameral administration, or intravitreal administration have not been established. Intraperitoneal administration of vancomycin has been associated with peritonitis. Hemorrhagic occlusive retinal vasculitis (HORV), including permanent loss of vision, has occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery.

Hearing impairment, ototoxicity, tinnitus

Vancomycin administration is associated with a risk for ototoxicity. Vancomycin should be used with caution in patients with underlying hearing impairment or tinnitus. The manufacturer recommends serial auditory function tests while patients receive vancomycin. Ototoxicity (hearing impairment or loss) has been reported with vancomycin therapy and may be transient or permanent. Factors that may increase the risk of developing ototoxicity include: excessive dose, underlying hearing loss, renal dysfunction, or multiple ototoxic drugs. The true incidence of ototoxicity is controversial. Early studies indicate a range of 1% to 9%; however, this rate may be inflated due to impurities associated with older formulations. The risk of ototoxicity from vancomycin monotherapy is low (without concurrent ototoxic agents). Severe ototoxicity is characterized by auditory nerve damage that initially affects high-frequency sensory hairs in the cochlea and then middle- and low-frequency hairs that can lead to total hearing loss. High-tone deafness occurs before low-tone deafness and is permanent. Reversible ototoxicity, such as tinnitus, can occur with or without high-tone deafness. Early studies attributed hearing loss to high vancomycin concentrations, but subsequent data suggest that there may be a lack of correlation between serum concentrations and ototoxicity.

Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken. Additionally, oral vancomycin should be used with caution in patients with inflammatory bowel disease. Oral vancomycin usually has poor absorption, but increased absorption and risk of toxicity may occur with these conditions.

Neonates, premature neonates

The clearance of vancomycin in neonates decreases as postconceptional age decreases, therefore, longer dosing intervals may be necessary in premature neonates.

Pregnancy

Data regarding intravenous vancomycin use in human pregnancy are not sufficient to inform a drug-associated risk; use with caution. Oral vancomycin acts primarily locally in the gastrointestinal tract and under usual circumstances is less likely to be absorbed into the maternal circulation than intravenous therapy. Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood levels in one newborn were about 76% of the mother's serum level after the mother received vancomycin 1 gram IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted. Evaluations of 10 cases where IV vancomycin 1 gram every 12 hours was administered to pregnant women for at least 1 week have shown no maternal nephrotoxicity or ototoxicity; adverse effects on renal function and hearing in the newborn were not observed. The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low. Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 gram IV every 12 hours for at least 1 week. Animal data does not show any risk of teratogenic or toxic effects on the fetus.

Breast-feeding

Vancomycin is excreted in human milk. Because of the potential for adverse effects, discontinue breast-feeding or discontinue vancomycin, taking into account the importance of the drug to the mother. It is not known if oral vancomycin is excreted in human breast milk, as no studies have been done. However, systemic absorption of vancomycin after oral administration is very low.

Geriatric

Geriatric patients may need monitoring and/or initial dosage adjustments because of a higher risk of toxicity and drug accumulation secondary to age-related decrease in renal function. Clinical studies with oral vancomycin demonstrated that geriatric patients are at an increased risk of nephrotoxicity during or after completion of therapy for pseudomembranous colitis. Additionally, patients older than 65 years of age may take longer to respond to therapy for Clostridium difficile; therefore, it is important for clinicians to be aware of the appropriate duration of therapy to avoid discontinuation or switching to alternative therapy prematurely. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral vancomycin must be accompanied by monitoring of renal function tests, including a baseline value, and serum vancomycin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. Use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

DRUG INTERACTIONS

Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as parenteral vancomycin, may decrease adefovir elimination by competing for common renal tubular transport systems, thereby increasing serum concentrations of adefovir and/or vancomycin. Additionally, chronic coadministration of adefovir with nephrotoxic drugs, such as vancomycin, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as vancomycin, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Alfentanil: (Moderate) The concurrent administration of vancomycin and anesthetics, like alfentanil, has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Amide local anesthetics: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Amikacin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Aminoglycosides: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs. Amphotericin B lipid complex (ABLC): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs. Amphotericin B liposomal (LAmB): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs. Amphotericin B: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs. Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as vancomycin, as the risk of renal impairment may be increased. Atracurium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Azelastine; Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Bacitracin: (Moderate) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations if these drugs must be used together. Beclomethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Benzonatate: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Beractant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants, such as beractant should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin. Betamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Bleomycin: (Minor) Previous treatment with nephrotoxic agents, like vancomycin, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior vancomycin therapy. Budesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Budesonide; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Calfactant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin. Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration of with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Celecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Cholestyramine: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible). Cholestyramine can bind other drugs, such as oral vancomycin, when given concurrently. Ciclesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Cidofovir: (Severe) The administration of cidofovir other potentially nephrotoxic agents, such as IV vancomycin, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir. Cisatracurium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Cisplatin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as cisplatin, can lead to additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Colesevelam: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 4 hours before colesevelam. Colesevelam can bind other drugs, such as oral vancomycin, when given concurrently. Colestipol: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 hours after colestipol (or as great an interval as possible). Colestipol can bind other drugs, such as oral vancomycin, when given concurrently. Colistimethate, Colistin, Polymyxin E: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered. Corticosteroids: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Corticotropin, ACTH: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Cortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Cyclosporine: (Minor) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including vancomycin, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly. Deflazacort: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Dexamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Diclofenac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Diclofenac; Misoprostol: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Diflunisal: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Diphenhydramine; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Diphenhydramine; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Donepezil; Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate. Doxacurium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Efavirenz; Emtricitabine; Tenofovir: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Entecavir: (Moderate) Vancomycin and entecavir both undergo renal tubular secretion. Monitor patients closely for adverse events when these drugs are coadministered. Elevated serum concentrations of either drug may occur. Esomeprazole; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Ester local anesthetics: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethacrynic Acid: (Major) Vancomycin should be used cautiously with other ototoxic drugs such as ethacrynic acid. Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Desogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Etonogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Etodolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Famotidine; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Fenoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Fentanyl: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Infusion-related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic induction. Fludrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Flunisolide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Flurbiprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Fluticasone; Salmeterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Fluticasone; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Formoterol; Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as parenteral vancomycin. Nephrotoxicity is also possible in patients receiving oral vancomycin for pseudomembranous colitis, should systemic absorption occur through significantly altered GI mucosa. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Furosemide: (Moderate) Vancomycin should be used cautiously with other ototoxic drugs such as furosemide. Gallium: (Severe) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as vancomycin, may increase the risk for developing severe renal insufficiency. If use of vancomycin is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of vancomycin is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl. Ganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. General anesthetics: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Gentamicin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Gold: (Minor) Both vancomycin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy. Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Hydrocodone; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Hydrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like vancomycin may increase the risk of developing nephrotoxicity. Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Ibuprofen; Oxycodone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Ibuprofen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Ifosfamide: (Moderate) Delayed renal clearance, and additive nephrotoxicity and neurotoxicity may occur in patients who have received or who are currently receiving nephrotoxic drugs and are now receiving ifosfamide. These drugs include IV vancomycin. Damaged kidney tubules may be less likely to convert mesna to its active kidney protecting form, which may contribute to the potential for increased ifosfamide toxicity. Clinicians should be alert for an increased risk of ifosfamide toxicity, including neurotoxicity, kidney toxicity, and bone marrow suppression. Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Indomethacin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Kanamycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Ketoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Ketorolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Lansoprazole; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision. Lorazepam: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Meclofenamate Sodium: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Mefenamic Acid: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Meloxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate. Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Methohexital: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Methotrexate: (Moderate) Recent exposure to vancomycin, in the absence of overt renal impairment, may adversely affect methotrexate excretion and increase risk of toxicity. Assessing renal function in patients who have received vancomycin may be prudent, so appropriate methotrexate dose modifications can be made. In a case report, two patients who had received a methotrexate-containing chemotherapy regimen initially displayed appropriate methotrexate clearance. However, administration of vancomycin in between chemotherapy treatment cycles appears to have caused markedly prolonged methotrexate clearance (i.e., 170 to 231 hours to reach serum methotrexate concentrations of less than 0.2 micro-M). Subclinical renal impairment was documented in both cases following vancomycin administration, which eventually resolved; subsequent methotrexate cycles, of the same dose, showed appropriate clearance. Methylprednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Mivacurium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Nabumetone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Naproxen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Naproxen; Sumatriptan: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Neuromuscular blockers: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Nonsteroidal antiinflammatory drugs: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Oxaprozin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, like vancomycin, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function. Pancuronium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Paromomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Pentamidine: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as systemic pentamidine, can lead to additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Piperacillin: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended. Piperacillin; Tazobactam: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended. Piroxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Polymyxin B: (Major) Systemic polymyxin B should not be used concurrently or sequentially with other drugs that have the potential for nephrotoxicity or neurotoxicity such as vancomycin. Topical products containing polymyxin B, especially when they are applied over a large body surface area, should be used cautiously with any of the above drugs. If concurrent systemic use is necessary, renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy. Polymyxins: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered. Poractant Alfa: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin. Prednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Prednisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Rapacuronium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Remifentanil: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Rocuronium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Rofecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as vancomycin, may lead to additive nephrotoxicity. Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Streptomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Streptozocin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drug, such as streptozocin, can lead to additive nephrotoxicity. Succinylcholine: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Sufentanil: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Sulindac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Tacrolimus: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as tacrolimus, can lead to additive nephrotoxicity. Monitor renal function closely and adjust vancomycin or tacrolimus doses according to serum concentrations. Telbivudine: (Moderate) Drugs that alter renal function such as vancomycin may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment. Tenofovir Alafenamide: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein. Tenofovir, PMPA: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Thiopental: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Tobramycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated. Tolmetin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis). Triamcinolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. Trospium: (Moderate) Both trospium and vancomycin are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or vancomycin due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or vancomycin is recommended. Tubocurarine: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Valdecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. Valganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with valganciclovir should be done cautiously to avoid additive nephrotoxicity. Vecuronium: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers. Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary. Zoledronic Acid: (Moderate) Coadministration of zoledronic acid with other potentially nephrotoxic drugs, such as vancomycin, may increase serum concentrations of either drug and increase the risk of nephrotoxicity. Monitor patients for changes in renal function if these drugs are coadministered.

PREGNANCY AND LACTATION

Pregnancy

Data regarding intravenous vancomycin use in human pregnancy are not sufficient to inform a drug-associated risk; use with caution. Oral vancomycin acts primarily locally in the gastrointestinal tract and under usual circumstances is less likely to be absorbed into the maternal circulation than intravenous therapy. Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood levels in one newborn were about 76% of the mother's serum level after the mother received vancomycin 1 gram IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted. Evaluations of 10 cases where IV vancomycin 1 gram every 12 hours was administered to pregnant women for at least 1 week have shown no maternal nephrotoxicity or ototoxicity; adverse effects on renal function and hearing in the newborn were not observed. The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low. Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 gram IV every 12 hours for at least 1 week. Animal data does not show any risk of teratogenic or toxic effects on the fetus.

Vancomycin is excreted in human milk. Because of the potential for adverse effects, discontinue breast-feeding or discontinue vancomycin, taking into account the importance of the drug to the mother. It is not known if oral vancomycin is excreted in human breast milk, as no studies have been done. However, systemic absorption of vancomycin after oral administration is very low.

MECHANISM OF ACTION

Vancomycin is bactericidal and appears to exert its effect by binding to the precursor units of bacterial cell walls, inhibiting their synthesis. It specifically binds with the D-alanyl-D-alanine terminus of the peptide precursor units, inhibiting peptidoglycan polymerase and transpeptidation reactions. This prevents cross-linking of the cell wall peptidoglycan during the second stage of cell synthesis. The net result is an alteration of bacterial cell wall permeability and cell death. In addition, RNA synthesis is inhibited. Vancomycin is not active in vitro to gram-negative organisms, mycobacteria, of fungi.

Vancomycin exhibits 'concentration-independent killing' in which there is saturation of the bacterial killing rate once the drug concentrations approach the minimum inhibitory concentration (MIC). Time-kill studies showed little difference in concentrations from 2—40 times the MIC. A study evaluating the area-under-the-curve and MIC (AUC:MIC), also known as area-under-the-inhibitory curve (AUIC), in an attempt to define efficacy parameters, showed patients with an AUC:MIC of < 125 had a higher probability of failure (p=0.004). A study in pneumonia patients specifically evaluating the relationship of AUC:MIC and vancomycin suggests there is a significant relationship between AUC:MIC and efficacy of vancomycin. Patients in this study with treatment cures averaged an AUC:MIC of 491 as compared to an average AUC:MIC of 306 for treatment failures. Since vancomycin has relatively poor penetration into respiratory secretions, this could account for the higher AUC:MIC necessary for success in this study. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) suggest that an AUC:MIC ratio of >= 400 is necessary to achieve clinical effectiveness with vancomycin. As AUC:MIC appears to be the major pharmacodynamic predictor for vancomycin, total antibiotic exposure is the key to a successful vancomycin regimen.

Most strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus sp., and Corynebacterium sp. are susceptible to vancomycin. Vancomycin is particularly useful against penicillin- and methicillin-resistant staphylococcal infections and for treating other gram-positive infections in beta-lactam-allergic patients. However, there are a few case reports of Staphylococcus aureus strains that are insensitive to vancomycin. While, traditionally, vancomycin has been used to treat enterococcal infections, there is a significant resistance rate in these organisms. Vancomycin-resistant enterococci (VRE) rates up to 12.1% have been reported in blood stream isolates and up to 25% of ICU enterococcal infections. Synergistic bactericidal effects can be achieved when vancomycin is combined with aminoglycosides against gram-positive organisms, but this increases possible toxicity. Vancomycin is useful against a wide variety of clinical infections due to these pathogens. When given orally, vancomycin is also useful in treating Clostridium difficile. Gram-negative bacteria and mycobacteria are resistant to vancomycin.

The manufacturer and the Clinical and Laboratory Standards Institute (CLSI) delineate the susceptibility interpretive criteria for vancomycin by pathogen. The MICs are defined for Enterococcus sp. and Coagulase-negative Staphylococcus sp. as susceptible <= 4 mcg/ml, intermediate 8—16 mcg/ml, and resistant >= 32 mcg/ml. For Staphylococcus aureus, the MIC breakpoints were lowered in 2006 and are defined as susceptible <= 2 mcg/ml, intermediate 4—8 mcg/ml, and resistant >= 16 mcg/ml. However, reports suggest that S. aureus isolates with vancomycin MICs of 1—2 mcg/ml may be less likely to be successfully treated with vancomycin. The defined MICs for Streptococcus sp., including Streptococcus pneumoniae, are susceptible <= 1 mcg/ml, with no definition for intermediate or resistant.

While vancomycin has been a predominant agent to treat gram-positive infections, increasing resistance has started to limit its utility. Vancomycin-resistant enterococci (VRE) is the most common resistant pathogen. There are six types of reported vancomycin resistance in enterococci (VanA, VanB, VanC, VanD, VanE, and VanG). Five of these types are acquired resistance, while VanC is an intrinsic resistance found in E. gallinarum and E. casseliflavus. The most common type is VanA resistance. Once exposed to an inducer, like vancomycin, transcription of the enzymes that make the cell-wall precursors is altered. There is an increase in the cell-wall precursors ending in D-alanyl-D-lactate, to which vancomycin has a low binding affinity, and a decrease in the D-alanyl-D-alanine cell-wall precursors, to which vancomycin has a high binding affinity. This results in decreased binding of vancomycin to the receptor sites of the enterococcal cell wall. The genes for this resistance can potentially be spread to other bacteria via plasmids. Exposure to IV and oral vancomycin, antianaerobic antibiotics, and other broad-spectrum antibiotics have all been associated as factors contributing to VRE. Staphylococcus aureus is another concerning organism with increasing resistance to vancomycin. Strains of vancomycin-intermediate S. aureus (VISA), heterogenous vancomycin-intermediate S. aureus (hVISA), and vancomycin-resistance S. aureus (VRSA) have been described in the literature. Strains of VISA have shown an unusually thickened cell wall that prevents drug penetration. The cell wall also contains dipeptides that bind vancomycin. Fully resistant strains, VRSA, have acquired VanA resistance similar to Enterococcus sp. The ASHP, IDSA, and SIDP suggest that exposure to vancomycin trough serum concentrations of < 10 mg/L may produce S. aureus strains with VISA-like characteristics.

PHARMACOKINETICS

In general, vancomycin is only administered intravenously although oral administration is important in the treatment of some GI infections such as pseudomembranous colitis. Vancomycin is not administered intramuscularly due to severe pain at the injection site.

Systemically administered vancomycin is distributed into most body tissues and fluids including pericardial fluid, pleural fluid, ascitic fluid, synovial fluid, urine, peritoneal dialysis fluid, and atrial appendage tissue. Concentrations obtained in tissues and fluids are variable and somewhat dependent on the degree of inflammation present. The volume of distribution coefficient is reported by the manufacturer as 0.3 to 0.43 L/kg; however, literature reports give a range of 0.2 to 1.9 L/kg. Unless the meninges are inflamed, there is little diffusion into CSF (0 to 3.45 mg/L) with corresponding CSF:serum ratios of 0 to 0.18. Inflamed meninges improve penetration into the CSF with reported concentrations of 6.4 to 11.1 mg/L with corresponding CSF:serum ratio of 0.36 to 0.46. Vancomycin is about 55% (range: 44% to 82%) bound to serum protein in healthy volunteers with normal renal function. There is no apparent metabolism of vancomycin. Excretion is mainly by glomerular filtration, with about 80% of the drug excreted in 24 hours in the urine and only small amounts excreted in the feces. In patients with normal renal function, vancomycin has a serum half-life of about 4 to 6 hours. Mean plasma clearance is approximately 0.058 L/kg/hour and mean renal clearance is approximately 0.048 L/kg/hour.

Oral Route

Oral bioavailability of vancomycin is too low to treat systemic infections; serum concentrations are often undetectable even when inflammatory lesions are present. Patients with pseudomembranous colitis, however, may develop detectable serum levels following oral administration, especially if they have renal impairment. Due to poor oral bioavailability, oral doses of vancomycin are excreted mainly in the feces (exceeding 100 mg/kg) with urinary recovery not exceeding 0.76% of the dose.

Intravenous Route

According to the manufacturer, after intravenous administration of 1,000 mg (15 mg/kg) over 1 hour, vancomycin plasma concentrations reach a peak of approximately 63 mcg/mL and fall to about 23 mcg/mL 2 hours after infusion, and 8 mcg/mL 11 hours after the end of the infusion. Multiple doses of 500 mg infused over 30 minutes produces mean serum concentrations of approximately 49 mcg/mL at the end of the infusion, 19 mcg/mL 2 hours after the infusion, and 10 mcg/mL 6 hours after the infusion. Vancomycin serum concentrations are highly variable and depend on many patient factors including age, size, fluid status, infection source/type, and renal function. Serum concentrations should be monitored individually to determine effective dosing.

Other Route(s)

Peritoneal RouteAccording to the manufacturer, approximately 60% of an intraperitoneal vancomycin dose, administered via intraperitoneal injection, is absorbed systemically in 6 hours. Serum concentrations of approximately 10 mcg/mL are achieved by an intraperitoneal dose of 30 mg/kg.

Rectal Route (Retention Enema)Similar to oral administration, patients with pseudomembranous colitis may develop detectable serum levels after rectal administration of retention enemas. Patients with renal impairment may be at a higher risk of systemic absorption.

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